B.I. Inborn Error of Metabolism Panel

Bruker IVDr for NewbornScreening (B.I.QUANT-UR ne)

Urine selective screening by NMR combines targeted analysis of metabolites including Inborn Error of Metabolism and other disease markers and non-targeted classification against healthy newborn models. Non-targeted screening enables the detection of all NMR-visible deviations from normal references, whether known or unknown. Figure 1 illustrates the identification of deviations from normality. All NMR spectra included inthereference model are combined in a so-called quantile plot, shown as a color band over the NMR spectrum. A spectrum from a new sample can be overlaid and tested for consistency with the model, i.e. all resonances will fit into the envelope defined by the model. This testing can be performed automatically in a uni- or multivariate fashion.The sample spectrum represents a canavan disease case. In the expansion of the overallNMR spectrum, signals of N-Acetylaspartic acidare clearly visible. As part of the B.I.QUANT-URpanel, N-Acetylaspartic acid can be identified andquantified automatically; however statistics would also reveal the existence of previously unseen deviations with the same certainty.

Influence of Metadata

Beside the use of normal models, it is also possible to investigate the influence of metadata on the NMR spectra. The influence of the day of life after birth on the NMR spectra has been especially investigated and the evolution of Metabolic Profile during the first days of lifecan be shown (figure 2). When new samples are projected onto this trajectory, it is possibleto determine whether the babies' development follows the model pattern. It is clear that sample B corresponds to a baby who has developed further than usual. Sample A is interesting because it comes from day 5 but falls into the group of day 1 and 2. This could indicate a delay in development and therefore advise further testing, as the delay could be the first sign of an inborn error not yet manifested by the usual biomarkers.

Support for Interpretation in Context of IEM
Bruker IVDr Inborn Error of Metabolism Panel ( B.I.IEM Panel)

The Bruker IVDr Inborn Errors of Metabolism Panel (B.I.IEM Panel), developed for research use only (RUO), automatically produces valuable support for the diagnostic interpretation of B.I.QUANT-UR results by using the database Metagene. Healthcare professionals can use the information in the context of diagnosis and management of inborn errors of metabolismin newborns, children and adults. The NMR metabolic findings of B.I.QUANT-UR can becompared against a dedicated Bruker version of Metagene's existing database which contains almost 1000 diseases and differential diagnoses,providing clinicians with a wealth of data tosupport diagnoses. Interactively, it is possible to add clinical relevant information which could help for the ranking of potential diagnoses. This panel approach not only supports diagnostics of inborn errors of metabolism but also research in the Pediatrics field.